Helminths revive to survive

Abstract

Helminth parasites are well known to have co-evolved a diverse arsenal of immunomodulatory factors to aid their persistence following infection. In this issue, Karo-Atar et al. (2022. J. Exp. Med.https://doi.org/10.1084/jem.20212311) demonstrate that products released by the gut-dwelling helminth Heligmosomoides polygyrus barkeri modify intestinal stem cells into a "revival" state, which is associated with a loss of helminth-expelling secretory cell types from the epithelium.

Insights from John R. Grainger and Rufus H. Daw.

Terminal differentiation of ISCs drives epithelial cell and secretory lineage repopulation of the intestinal villus at homeostasis. Following intestinal damage, for example during Hpb larval infiltration, IFN-γ–dependent fetal-like reversion of Sca-1⁺ ISCs occurs. Adult-stage Hpb infection in the intestinal lumen co-opts this type of response to intestinal damage via its ES products. The ES favors the differentiation of activated fetal-like Clu⁺ revSCs and reduces development of IL-4/IL-13 responsive immunologically involved epithelial cell lineages, such as goblet cells, important in worm expulsion. Created with BioRender.com.